Increased Neuronal Excitability, Synaptic Plasticity, and Learning in Aged Kvβ1.1 Knockout Mice

Murphy, Geoffrey G.; Fedorov, N. A.; Giese, K. Peter; Ohno, Minoru; Friedman, Eugenia; Chen, Rachel; Silva, Alcino J.

doi:10.1016/j.cub.2004.10.021

Cited by 95 publications

(80 citation statements)

References 41 publications

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“…Kv␤1.1-deficient mice show normal synaptic plasticity, but they show impaired learning, indicating that the Kv ␤1.1-subunit contributes to certain types of learning and memory (53). In aged mice, the deletion of the auxiliary potassium channel subunit Kv␤1.1 resulted in increased neuronal excitability, synaptic plasticity, and learning (55). The phenotype of Kv␤2-null mice includes reduced life spans, occasional seizures, and cold swim-induced tremors similar to that observed in Kv1.1-null mice (54).…”

Section: Knock-out Modelsmentioning

confidence: 94%

A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

Torres

Morera

Carvacho

et al. 2007

Journal of Biological Chemistry

107

103

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The movement of ions across cell membranes is essential for a wide variety of fundamental physiological processes, including secretion, muscle contraction, and neuronal excitation. This movement is possible because of the presence in the cell membrane of a class of integral membrane proteins dubbed ion channels. Ion channels, thanks to the presence of aqueous pores in their structure, catalyze the passage of ions across the otherwise ion-impermeable lipid bilayer. Ion conduction across ion channels is highly regulated, and in the case of voltage-dependent K

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Section: Knock-out Modelsmentioning

confidence: 94%

A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

Torres

Morera

Carvacho

et al. 2007

Journal of Biological Chemistry

107

103

View full text Add to dashboard Cite

show abstract

“…The few cases in which loss-offunction mutations led to improved spatial learning and memory include mutations that increase neuronal excitability (Collinson et al, 2002;Murphy et al, 2004;Nolan et al, 2004) or that affect synaptic calcium dynamics (Futatsugi et al, 1999;Jeon et al, 2003) (see below). In these cases, changes in long-term memory retention were not fully addressed.…”

Section: Shank1 Deletion Genetically Dissociates Hippocampus-dependenmentioning

confidence: 99%

Smaller Dendritic Spines, Weaker Synaptic Transmission, but Enhanced Spatial Learning in Mice Lacking Shank1

et al. 2008

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Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders.

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Section: K V Channels and Learning And Memorymentioning

confidence: 99%

“…Deletion of the K v β1.1 subunit gene results in reduced I A amplitude, increased neuronal excitability, improved Morris water maze performance, and a decreased threshold for the induction of LTP (Giese et al 1998;Murphy et al 2004). K v β1.1-deficient mice also exhibit reductions in both frequency-dependent spike broadening and the slow after hyperpolarization, modulation of which has been proposed as a learning and memory mechanism (Giese et al 1998(Giese et al , 2001Murphy et al 2004). Meanwhile, clusters of K v 2.1 channels account for the somatodendritic I K (Murakoshi and Trimmer 1999;Du et al 2000;Pal et al 2003) and are necessary for regulating both intrinsic and neuronal excitability during high-frequency stimulation (Du et al 2000;Misonou et al 2005).…”

Section: K V Channels and Learning And Memorymentioning

confidence: 99%

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Keblesh

Xiong

2008

J Neuroimmune Pharmacol

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Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD), a severe form of HIV-associated neurocognitive disorders (HAND), describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (brain perivascular macrophages and microglia) releasing immune and viral products in the brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates voltage-gated potassium (K v ) channels, key regulators of cell excitability and animal behavior (learning and memory), are involved in the pathogenesis of HAD/HAND. Here we survey the literature and find that HAD-related alterations in cellular and viral products can increase neuronal K v channel activity, leading to neuronal dysfunction and cognitive deficits. Thus, neuronal K v channels may be a new target in the effort to develop therapies for HAD and perhaps other inflammatory neurodegenerative disorders.

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Increased Neuronal Excitability, Synaptic Plasticity, and Learning in Aged Kvβ1.1 Knockout Mice

Abstract: Neuronal excitability is an important determinant of both synaptic plasticity and learning in aged subjects.

Cited by 95 publications

References 41 publications

A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

Smaller Dendritic Spines, Weaker Synaptic Transmission, but Enhanced Spatial Learning in Mice Lacking Shank1

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

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